関: omega-conotoxin MVIIA

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/05 20:00:51」(JST)

wiki en

Ziconotide (SNX-111; Prialt) is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from Conus magus (Cone Snail), it is the synthetic form of an ω-conotoxin peptide.^[1]

In December 2004 the Food and Drug Administration approved ziconotide when delivered as an infusion into the cerebrospinal fluid using an intrathecal pump system.

§Discovery

Ziconotide is derived from the toxin of the cone snail species Conus magus. Scientists have been intrigued by the effects of the thousands of chemicals in marine snail toxins since the initial investigations in the late 1960s by Baldomero Olivera. Olivera, now a professor of biology in the University of Utah, was inspired by accounts of the deadly effects of these toxins from his childhood in the Philippines. Ziconotide was discovered in the early 1980s by University of Utah research scientist Michael McIntosh,^[2] when he was barely out of high school and working with Baldomero Olivera.^[3]

Ziconotide was developed into an artificially manufactured drug by Elan Corporation. It was approved for sale under the name Prialt by the U.S. Food and Drug Administration on December 28, 2004, and by the European Commission on February 22, 2005. Azur Pharma acquired worldwide rights (except Europe) to Prialt in 2010.

§Mechanism of action

Ziconotide is a hydrophilic molecule that is freely soluble in water and is practically insoluble in methyl t-butyl ether. Ziconotide acts as a selective N-type voltage-gated calcium channel blocker.^[4]^[5] This action inhibits the release of pro-nociceptive neurochemicals like glutamate, calcitonin gene-related peptide (CGRP), and substance P in the brain and spinal cord, resulting in pain relief.^[5]

§Therapeutic use

Due to the profound side effects or lack of efficacy when delivered through more common routes, such as orally or intravenously, ziconotide must be administered intrathecally (i.e. directly into the spinal fluid). As this is the most expensive and invasive method of drug delivery and involves additional risks of its own,^[6] ziconotide therapy is generally considered appropriate (as evidenced by the range of use approved by the FDA in US) only for “management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine”.^[7] In practice, the efficacy of ziconotide in relieving neurogenic pain remains to be established, according to Prescrire International, October 2008. Furthermore "It is better to re-examine and, if possible, correct the reasons for opiate treatment failure rather than prescribe ziconotide."

However, this must be weighed against the high level of pain management, both in terms of degree and length, and the apparent lack of tolerance^[8] and other signs of dependence^[9] even after extended treatment along with the need for alternatives to other therapies that have not worked for the patient. Ziconotide is also contraindicated for patients with certain preexisting mental disorders (e.g. psychosis) due to evidence that they are more susceptible to certain severe side effects.^[10]

§Adverse reactions

The most common side effects are dizziness, nausea, confusion, nystagmus and headache. Others may include weakness, hypertonia, ataxia, abnormal vision, anorexia, somnolence, unsteadiness on feet, vertigo, urinary retention, pruritis, increased sweating, diarrhea, nausea, vomiting, asthenia, fever, rigors, sinusitis, muscle spasms, myalgia, insomnia, anxiety, amnesia, nystagmus, tremor, memory impairment and induced psychiatric disorders. Other side effects which are less frequent but still clinically significant include auditory and visual hallucinations, thoughts of suicide, acute renal failure, atrial fibrilation, cardiovascular accident, sepsis, new or worsening depression, paranoia, disorientation, meningitis and seizures. Therefore, it is contraindicated in people with a history of psychosis, schizophrenia, clinical depression, and bipolar disorder. Recent incidents suggesting a link between intrathecal ziconotide treatment and increased risk of suicide have led to calls for strict and ongoing psychiatric monitoring of patients to avoid suicide occurring in vulnerable individuals.^[11] There is no known antidote.

§Structure

Ziconotide is a peptide with the amino acid sequence H-Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-NH₂

§Patents

The drug was patented by Neurex Corp., a U.S. company purchased in 1998 by Élan Corporation, plc of Ireland. U.S. patents assigned to Elan include 5,859,186, 5,795,864, 5,770,690, 5,587,454, and 5,559,095.

§See also

Leconotide
Ralfinamide
Lacosamide, approved for partial-onset seizures and diabetic neuropathic pain

§References

^ Skov MJ, Beck JC, de Kater AW, Shopp GM (2007). "Nonclinical safety of ziconotide: an intrathecal analgesic of a new pharmaceutical class". Int. J. Toxicol. 26 (5): 411–21. doi:10.1080/10915810701582970. PMID 17963128.
^ McIntosh M, Cruz LJ, Hunkapiller MW, Gray WR, Olivera BM (1982). "Isolation and structure of a peptide toxin from the marine snail Conus magus". Arch. Biochem. Biophys. 218 (1): 329–34. doi:10.1016/0003-9861(82)90351-4. PMID 7149738.
^ "NIGMS – Findings, September 2002: Secrets of the Killer Snails". Retrieved 2007-12-21.
^ Miljanich GP (2004). "Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.". Curr Med Chem 11 (23): 3029–40. doi:10.2174/0929867043363884. PMID 15578997.
^ ^a ^b McGivern JG (2007). "Ziconotide: a review of its pharmacology and use in the treatment of pain.". Neuropsychiatr Dis Treat 3 (1): 69–85. doi:10.2147/nedt.2007.3.1.69. PMC 2654521. PMID 19300539.
^ "Medscape". Retrieved 2007-12-21.
^ "U.S. Pharmacist". Retrieved 2007-12-21.
^ Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today 42 (6): 369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.
^ Klotz U (2006). "Ziconotide—a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain—a short review". Int J Clin Pharmacol Ther 44 (10): 478–83. PMID 17063978.
^ prialt.com
^ Maier C, Gockel HH, Gruhn K, Krumova EK, Edel MA (October 2010). "Increased risk of suicide under intrathecal ziconotide treatment? – A warning". Pain 152 (1): 235–237. doi:10.1016/j.pain.2010.10.007. PMID 21041028.

§External links

Manufacturer website
FDA approves new drug for severe pain, a December 2004 Associated Press article
Press release announcing FDA approval from Elan
Ziconotide Effectiveness and Safety Trial in Patients with Chronic Severe Pain

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 慢性疼痛の治療の概要 overview of the treatment of chronic pain
2. 癌疼痛のマネージメント：介入的治療 cancer pain management interventional therapies
3. 亜急性および慢性腰痛：外科治療 subacute and chronic low back pain surgical treatment

English Journal

Influence of pH and temperature on ziconotide stability in intrathecal analgesic admixtures in implantable pumps and syringes.

Bazin C1, Poirier AL2, Dupoiron D3.
International journal of pharmaceutics.Int J Pharm.2015 Jun 20;487(1-2):285-91. doi: 10.1016/j.ijpharm.2015.04.041. Epub 2015 Apr 16.
PURPOSE: The aim of our study was to investigate the influence of pH and temperature on the stability of ziconotide in analgesic admixtures containing morphine and ropivacaine.METHODS: All admixtures were combined using a wide range of concentrations, in implantable pumps and syringes, using tempera
PMID 25891257

Suppression of Peripheral Pain by Blockade of Voltage-Gated Calcium 2.2 Channels in Nociceptors Induces RANKL and Impairs Recovery From Inflammatory Arthritis in a Mouse Model.

Baddack U1, Frahm S2, Antolin-Fontes B3, Grobe J4, Lipp M4, Müller G4, Ibañez-Tallon I3.
Arthritis & rheumatology (Hoboken, N.J.).Arthritis Rheumatol.2015 Jun;67(6):1657-67. doi: 10.1002/art.39094.
OBJECTIVE: A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies inflammation and joint deformation. Patients with RA rate pain relief as the highest priority; however, few studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways.
PMID 25733371

A perspective on toxicology of Conus venom peptides.

Kumar PS1, Kumar DS2, Umamaheswari S3.
Asian Pacific journal of tropical medicine.Asian Pac J Trop Med.2015 May;8(5):337-51. doi: 10.1016/S1995-7645(14)60342-4.
The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery. The focus of this investigation is to summarize the worldwide distribution of Conus and their species diversity with special reference to the Indi
PMID 26003592

Japanese Journal

Suppression of Formalin-Induced Nociception by Cilnidipine, a Voltage-Dependent Calcium Channel Blocker

Biological and Pharmaceutical Bulletin 32(10), 1695-1700, 2009
NAID 130000116929

Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain

Reg Anesth Pain Med 25, 274-278, 2000
NAID 30015148924

An evaluation of intrathecal ziconotide for the treatment of chronic pain

Expert Opin Investig Drugs 9, 2403-2410, 2000
NAID 30009877138

Related Pictures

★リンクテーブル★

リンク元	「ジコノチド」「omega-conotoxin MVIIA」

「ジコノチド」

Ziconotide
Systematic (IUPAC) name
	?
Clinical data
AHFS/Drugs.com	monograph
Pregnancy; category	US: C;
Legal status	℞ Prescription only;
Routes	Intrathecal – directly into cerebrospinal fluid by a catheter
Pharmacokinetic data
Bioavailability	50%
Metabolism	?
Half-life	2.9 to 6.5 hours
Excretion	<1% urine
Identifiers
CAS number	107452-89-1
ATC code	N02BG08
PubChem	CID 16135415
IUPHAR ligand	5364
ChemSpider	17291932
UNII	7I64C51O16
KEGG	D06363
ChEMBL	CHEMBL1201418
Chemical data
Formula	C102H172N36O32S7
Molecular mass	2639 daltons
	SMILES C[C@H]1C(=O)N[C@H](C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)NCC(=O)N1)CCCCN)CCCCN)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N3)CO)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)CO)CCCNC(=N)N)CC(C)C)CCSC)CC4=CC=C(C=C4)O)CC(=O)O)C(=O)N)CCCCN)CO)CCCNC(=N)N)CCCCN;
	InChI InChI=1S/C102H172N36O32S7/c1-50(2)34-63-91(161)127-62(26-33-171-5)90(160)129-64(35-53-22-24-54(143)25-23-53)92(162)130-65(36-78(148)149)93(163)135-72-48-175-173-45-69(80(108)150)133-86(156)58(18-8-12-29-105)121-76(146)39-117-85(155)66(41-139)131-88(158)61(21-15-32-114-102(111)112)126-96(166)70-46-176-177-47-71(97(167)132-68(43-141)95(165)125-60(87(157)128-63)20-14-31-113-101(109)110)134-89(159)59(19-9-13-30-106)123-81(151)51(3)119-74(144)37-115-83(153)56(16-6-10-27-103)120-75(145)38-116-84(154)57(17-7-11-28-104)124-82(152)55(107)44-172-174-49-73(137-98(72)168)99(169)138-79(52(4)142)100(170)118-40-77(147)122-67(42-140)94(164)136-70/h22-25,50-52,55-73,79,139-143H,6-21,26-49,103-107H2,1-5H3,(H2,108,150)(H,115,153)(H,116,154)(H,117,155)(H,118,170)(H,119,144)(H,120,145)(H,121,146)(H,122,147)(H,123,151)(H,124,152)(H,125,165)(H,126,166)(H,127,161)(H,128,157)(H,129,160)(H,130,162)(H,131,158)(H,132,167)(H,133,156)(H,134,159)(H,135,163)(H,136,164)(H,137,168)(H,138,169)(H,148,149)(H4,109,110,113)(H4,111,112,114)/t51-,52+,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,79-/m0/s1 ; Key:BPKIMPVREBSLAJ-QTBYCLKRSA-N ;
(what is this?) (verify)

　　[★]

英: ziconotide
関: ω-コノトキシンMVIIA

「omega-conotoxin MVIIA」

　　[★]

ωコノトキシンMVIIA

関: ziconotide

[pmid17963128-1] Skov MJ, Beck JC, de Kater AW, Shopp GM (2007). "Nonclinical safety of ziconotide: an intrathecal analgesic of a new pharmaceutical class". Int. J. Toxicol. 26 (5): 411–21. doi:10.1080/10915810701582970. PMID 17963128.

[pmid7149738-2] McIntosh M, Cruz LJ, Hunkapiller MW, Gray WR, Olivera BM (1982). "Isolation and structure of a peptide toxin from the marine snail Conus magus". Arch. Biochem. Biophys. 218 (1): 329–34. doi:10.1016/0003-9861(82)90351-4. PMID 7149738.

[titleNIGMS_--_Findings.2C_September_2002:_Secrets_of_the_Killer_Snails-3] "NIGMS – Findings, September 2002: Secrets of the Killer Snails". Retrieved 2007-12-21.

[pmid15578997-4] Miljanich GP (2004). "Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.". Curr Med Chem 11 (23): 3029–40. doi:10.2174/0929867043363884. PMID 15578997.

[pmid19300539-5] McGivern JG (2007). "Ziconotide: a review of its pharmacology and use in the treatment of pain.". Neuropsychiatr Dis Treat 3 (1): 69–85. doi:10.2147/nedt.2007.3.1.69. PMC 2654521. PMID 19300539.

[6] "Medscape". Retrieved 2007-12-21.

[titleU.S._Pharmacist-7] "U.S. Pharmacist". Retrieved 2007-12-21.

[pmid16845440-8] Prommer E (2006). "Ziconotide: a new option for refractory pain". Drugs Today 42 (6): 369–78. doi:10.1358/dot.2006.42.6.973534. PMID 16845440.

[pmid17063978-9] Klotz U (2006). "Ziconotide—a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain—a short review". Int J Clin Pharmacol Ther 44 (10): 478–83. PMID 17063978.

[10] rialt.com

[pmid21041028-11] Maier C, Gockel HH, Gruhn K, Krumova EK, Edel MA (October 2010). "Increased risk of suicide under intrathecal ziconotide treatment? – A warning". Pain 152 (1): 235–237. doi:10.1016/j.pain.2010.10.007. PMID 21041028.

匿名

検索

案内

案内

ziconotide